Neurology Flashcards
A stroke is also referred to as cerebrovascular accident (CVA). CVA’s are either ?
- Ischaemia or infarction of brain tissue secondary to inadequate blood supply
- Intracranial haemorrhage
In regards to a CVA, disruption of blood supply can be caused by ? (4 points)
- Thrombus formation or embolus, for example in patients with atrial fibrillation
- Atherosclerosis
- Shock
- Vasculitis
Note:
Transient ischaemic attack (TIA) was originally defined as symptoms of a stroke that resolve within 24 hours. It has been updated based on advanced imaging to now be defined as transient neurological dysfunction secondary to ischaemia without infarction.
TIA’s often precede a full a stroke. What is a crescendo TIA ?
Where there are two or more TIAs within a week.
Note: This carries a high risk of developing in to a stroke.
In neurology, suspect a vascular cause where there is a sudden onset of neurological symptoms. What are the symptoms of a stroke ?
Stoke symptoms are typically asymmetrical:
- Sudden weakness of limbs
- Sudden facial weakness
- Sudden onset dysphasia (speech disturbance)
- Sudden onset visual or sensory loss
RF’s for a stroke ? (10 points)
- Cardiovascular disease such as angina, myocardial infarction and peripheral vascular disease
- Previous stroke or TIA
- Atrial fibrillation
- Carotid artery disease
- Hypertension
- Diabetes
- Smoking
- Vasculitis
- Thrombophilia
- Combined contraceptive pill
FAST tool for identifying a stroke in the community ?
F – Face
A – Arm
S – Speech
T – Time (act fast and call 999)
What is the ROSIER tool + what does it indicate ?
Tool for Recognition Of Stroke In Emergency Room.
Stroke is likely if the pt scores anything above a 0.
Tool used for assessing pts with a suspected TIA to estimate their risk of subsequently having a stroke + what are its components ?
ABCD2 score
A - Age (>60 = 1)
B - Blood pressure (>140/90 = 1)
C - Clinical features (unilateral weakness = 2, dysphasia without weakness = 1)
D - Duration (more than 60 minutes = 2, 10 to 60 minutes = 1, less than 10 minutes = 0)
D - Diabeters = 1
Management of a stroke ?
- Admit pts to a specialist stroke centre
- Exclude hypoglycaemia
- Immediate CT brain to exclude primary intracerebral haemorrhage
- Aspirin 300mg stat (after the CT) and continued for 2 weeks
- Thrombolysis with alteplase can be used after the CT brain scan has excluded an intracranial haemorrhage. Alteplase is a tissue plasminogen activator that rapidly breaks down clots and can reverse the effects of a stroke if given in time. It is given based on local protocols by an experienced physician. It needs to be given within a defined window of opportunity, for example 4.5 hours. Patients need monitoring for post thrombolysis complications such as intracranial or systemic haemorrhage. This includes using repeated CT scans of the brain.
- Thrombectomy (mechanical removal of the clot) may be offered if an occlusion is confirmed on imaging, depending on the location and the time since the symptoms started. It is not used after 24 hours since the onset of symptoms.
Note: Generally, blood pressure should not be lowered during a stroke because this risks reducing the perfusion to the brain.
Management of TIA ?
-Start aspirin 300mg daily. Start secondary prevention measures for cardiovascular disease. They should be referred and seen within 24 hours by a stroke specialist.
Specialist imaging used to investigate strokes / TIAs + what is the aim of this imaging ?
- The aim of imaging is to establish the vascular territory that is affected. It is guided by specialist assessment.
- Diffusion-weighted MRI is the gold standard imaging technique. CT is an alternative.
- Carotid ultrasound can be used to assess for carotid stenosis. Endarterectomy to remove plaques or carotid stenting to widen the lumen should be considered if there is carotid stenosis.
Secondary prevention of stroke ? (4 points)
- Clopidogrel 75mg once daily (alternatively dipyridamole 200mg twice daily)
- Atorvastatin 80mg should be started but not immediately
- Carotid endarterectomy or stenting in patients with carotid artery disease
- Treat modifiable risk factors such as hypertension and diabetes
Stroke rehabilitation ?
Once patients have had a stroke they require a period of adjustment and rehabilitation. This is an essential and central to stroke care. It involves a multidisciplinary team including:
- Nurses
- Speech and language (SALT)
- Nutrition and dietetics
- Physiotherapy
- Occupational therapy
- Social services
- Optometry and ophthalmology
- Psychology
- Orthotics
Around 10-20% of strokes are caused by intracranial bleeds. Name 6 RF’s ?
- Head injury
- Hypertension
- Aneurysms
- Ischaemic stroke can progress to haemorrhage
- Brain tumours
- Anticoagulants such as warfarin
Presentation of intracranial bleeds ? (include key feature)
Sudden onset headache is a key feature. They can also present with:
- Seizures
- Weakness
- Vomiting
- Reduced consciousness
- Other sudden onset neurological symptoms
In terms of a pts GCS, when do you need to consider securing their airway ?
When someone has a score of 8 or below.
What causes a subdural haemorrhage + where do they occur, what would a CT scan show and in which pts do they occur more frequently + why ?
- Subdural haemorrhage is caused by rupture of the bridging veins in the outermost meningeal layer. They occur between the dura mater and arachnoid mater.
- On a CT scan they have a crescent shape and are not limited by the cranial sutures (they can cross over the sutures).
- Subdural haemorrhages occur more frequently in elderly or alcoholic patients. These patients have more atrophy in their brains making vessels more likely to rupture.
What causes an extradural haemorrhage, what is it associated with, where does it occur, what would a CT scan show ?
- Extradural haemorrhage is usually caused by rupture of the middle meningeal artery in the temporo-parietal region.
- It can be associated with a fracture of the temporal bone.
- It occurs between the skull and dura mater.
- On a CT scan they have a bi-convex shape and are limited by the cranial sutures (they can’t cross over the sutures).
Note:
The typical history for someone presenting with an extradural haemorrhage is a young patient with a traumatic head injury that has an ongoing headache. They have a period of improved neurological symptoms and consciousness followed by a rapid decline over hours as the haematoma gets large enough to compress the intracranial contents.
Intracerebral haemorrhage involves bleeding into the brain tissue. How does it present ?
It presents similarly to an ischaemic stroke.
Note: These can be anywhere in the brain tissue:
- Lobar intracerebral haemorrhage
- Deep intracerebral haemorrhage
- Intraventricular haemorrhage
- Basal ganglia haemorrhage
- Cerebellar haemorrhage
They can occur spontaneously or as the result of bleeding into an ischaemic infarct or tumour or rupture of an aneurysm.
Principles of managing an intracranial bleed ?
- Immediate CT head to establish the diagnosis
- Check FBC and clotting
- Admit to a specialist stroke unit
- Discuss with a specialist neurosurgical centre to consider surgical treatment
- Consider intubation, ventilation and ICU care if they have reduced consciousness
- Correct any clotting abnormality
- Correct severe hypertension but avoid hypotension
Subarachnoid haemorrhage involves bleeding in to the subarachnoid space, where the cerebrospinal fluid is located, between the pia mater and the arachnoid membrane. This is usually the result of what ?
A ruptured cerebral aneurysm.
Note:
Subarachnoid haemorrhage has a very high mortality and morbidity. It is very important not to miss the diagnosis and you need to have a low suspicion to trigger full investigations. It needs to be discussed with the neurosurgical unit with a view to surgical intervention.
The typical history of a subarachnoid haemorrhage is a sudden onset occipital headache that occurs during strenuous activity such as weight lifting or sex. This occurs so suddenly that it is known as a what + name 3 other features ?
A thunderclap headache. It is is described like being hit really hard on the back of the head.
Other features are:
- Neck stiffness
- Photophobia
- Neurological symptoms such as visual changes, speech changes, weakness, seizures and loss of consciousness
Name 5 RF’s for a SAH ?
- Hypertension
- Smoking
- Excessive alcohol consumption
- Cocaine use
- Family history
SAH is more common in ? (3 points)
- Black patients
- Female patients
- Age 45-70
SAH is particularly associated with ? (5 points)
- Cocaine use
- Sickle cell anaemia
- Connective tissue disorders (such as Marfan syndrome or Ehlers-Danlos)
- Neurofibromatosis
- Autosomal dominant polycystic kidney disease
Investigations for SAH + what will they show ?
CT head is the first line investigation. Immediate CT head is required. Blood will cause hyperattenuation in the subarachnoid space.
Lumbar puncture is used to collect a sample of the cerebrospinal fluid if the CT head is negative. CSF can be tested for signs of subarachnoid haemorrhage:
- Red cell count will be raised. If the cell count is decreasing in number over the samples, this could be due to a traumatic lumbar puncture.
- Xanthochromia (the yellow colour of CSF caused by bilirubin)
Angiography (CT or MRI) can be used once a subarachnoid haemorrhage is confirmed to locate the source of the bleeding.
Management of a SAH ? (5 points)
- Patients should be managed by a specialist neurosurgical unit. Patients with reduced consciousness may require intubation and ventilation. Supportive care as part of a multi-disciplinary team is important with good nursing, nutrition, physiotherapy and occupational therapy involved during the initial stages and recovery.
- Surgical intervention may be used to treat aneurysms. The aim is to repair the vessel and prevent re-bleeding. This can done by coiling, which involves inserting a catheter into the arterial system (taking an “endovascular approach”), placing platinum coils into the aneurysm and sealing it off from the artery. An alternative is clipping, which involves cranial surgery and putting a clip on the aneurysm to seal it.
- Nimodipine is a calcium channel blocker that is used to prevent vasospasm. Vasospasm is a common complication that can result in brain ischaemia following a subarachnoid haemorrhage.
- Lumbar puncture or insertion of a shunt may be required to treat hydrocephalus.
- Antiepileptic medications can be used to treat seizures.
What is MS + what causes it ?
Multiple sclerosis (MS) is a chronic and progressive condition that involves demyelination of the myelinated neurones in the central nervous system.
This is caused by an inflammatory process involving activation of immune cells against the myelin.
Note:
MS typically presents in young adults (under 50 years) and is more common women. Symptoms tend to improving in pregnancy and in the postpartum period.
Pathophysiology of MS ?
Myelin covers the axons of neurones in the central nervous system. This myelin helps the electrical impulse move faster along the axon. Myelin is provided by cells that wrap themselves around the axons. These are Schwann cells in the peripheral nervous system and oligodendrocytes in the central nervous system.
Multiple sclerosis typically only affects the central nervous system (the oligodendrocytes). There is inflammation around myelin and infiltration of immune cells that cause damage to the myelin. This affects the way electrical signals travel along the nerve leading to the symptoms of multiple sclerosis.
When a patient presents with symptoms of a clinical “attack” of MS, for example an episode of optic neuritis, there are usually other lesions of demyelination at the same time throughout the central nervous system, most of which are not causing symptoms.
In early disease, re-myelination can occur and symptoms can resolve. In the later stages of the disease, re-myelination is incomplete and symptoms gradually become more permanent.
A characteristic features of MS is that lesions vary in their location over time, meaning that different nerves are affected and symptoms change over time. The key expression to remember to describe the way MS lesions change location over time is that they are “disseminated in time and space”.
Cause of MS ?
The cause of the demyelination is unclear, but there is growing evidence that it is influenced by a combination of:
- Multiple genes
- Epstein–Barr virus (EBV)
- Low vitamin D
- Smoking
- Obesity
Signs + symptoms of MS ?
Symptoms usually progress over more than 24 hours. At the first presentation symptoms tend to last days to weeks and then improve. There are a number of ways MS can present. These are described below.
-Optic neuritis
Eye movement abnormalities:
- May present with diplopia (due to lesions affecting CN VI)
- Internuclear opthalmoplegia
- Conjugate lateral gaze disorder
Focal weakness:
- Bells palsy
- Horners syndrome
- Limb paralysis
- Incontinence
Focal sensory symptoms
-Trigeminal neuralgia
-Numbness
-Paraesthesia (pins and needles)
-Lhermitte’s sign is an electric shock sensation travels down the spine and into the limbs when flexing the neck.
It indicates disease in the cervical spinal cord in the dorsal column. It is caused by stretching the demyelinated dorsal column.
Ataxia:
Ataxia is a problem with coordinated movement. It can be sensory or cerebellar:
- Sensory ataxia is the result of loss of the proprioceptive sense, which is the ability to sense the position of the joint (e.g. is the joint flexed or extended). This results in a positive Romberg’s test and can cause pseudoathetosis.
- Cerebellar ataxia is the result of problems with the cerebellum coordinating movement. This suggestions cerebellar lesions.
Disease patterns of MS note :
The disease course is highly variable between individuals. Some patients may have mild relapsing-remitting episodes for life whereas others have primary progressive MS that progresses without any improvement in symptoms. There are certain classifications used to describe the pattern of MS in an individual. These patterns are not separate conditions but part of a spectrum of disease activity.
Clinically Isolated Syndrome
This describes the first episode of demyelination and neurological signs and symptoms. MS cannot be diagnosed on one episode as the lesions have not been “disseminated in time and space”. Patients with clinically isolated syndrome may never have another episode or develop MS. If lesions are seen on MRI scan then they are more likely to progress to MS.
Relapsing-Remitting
Relapsing-remitting MS is the most common pattern at initial diagnosis. It is characterised by episodes of disease and neurological symptoms followed by recovery. In MS the symptoms occur in different areas with different episodes. This can be further classified based on whether the disease is active and/or worsening:
Active: new symptoms are developing or new lesions are appearing on MRI
Not active: no new symptoms or MRI lesions are developing
Worsening: there is an overall worsening of disability over time
Not worsening: there is no worsening of disability over time
Secondary Progressive
Secondary progressive MS is where there was relapsing-remitting disease at first, but now there is a progressive worsening of symptoms with incomplete remissions. Symptoms become more and more permanent. Secondary progressive MS can be further classified based on whether the disease is active and/or progressing.
Active: new symptoms are developing or new lesions are appearing on MRI
Not active: no new symptoms or MRI lesions are developing
Progressing: there is an overall worsening of disease over time (regardless of relapses)
Not progressing: there is no worsening of disease over time
Primary Progressive
Primary progressive MS is where there is a worsening of disease and neurological symptoms from the point of diagnosis without initial relapses and remissions. This can be further classified in a similar way to secondary progressive based on whether it is active and/or progressing.
Diagnosis of MS (include investigations) ?
Diagnosis is made by a neurologist based on the clinical picture and symptoms suggesting lesions that change location over time. Symptoms have to be progressive over a period of 1 year to diagnose primary progressive MS. Other causes for the symptoms need to be excluded.
Investigations can support the diagnosis:
- MRI scans can demonstrate typical lesions
- Lumbar puncture can detect “oligoclonal bands” in the cerebrospinal fluid (CSF)
What is optic neuritis (include key features) ?
Optic neuritis presents with unilateral reduced vision developing over hours to days. Key features are:
- Central scotoma. This is an enlarged blind spot.
- Pain on eye movement
- Impaired colour vision
- Relative afferent pupillary defect
Multiple sclerosis is the main cause of optic neuritis, however it can also be caused by what (7 points) ?
- Sarcoidosis
- Systemic lupus erythematosus
- Diabetes
- Syphilis
- Measles
- Mumps
- Lyme disease
Note:
Patients presenting with acute loss of vision should be seen urgently by an ophthalmologist for assessment. It is treated with steroids and recovery takes 2-6 weeks. Around 50% of patients with a single episode of optic neuritis will go on to develop MS over the next 15 years. Changes on an MRI scan help to predict which patients will go on to develop MS.
Management of MS ?
Multiple sclerosis is managed by a specialist multidisciplinary team (MDT) including neurologists, specialist nurses, physiotherapy, occupational therapy and others. Patient should be fully educated about their condition and treatment.
Disease Modification
Treatment with disease-modifying drugs and biologic therapy has changed the management of multiple sclerosis so that the aim of treatment is now to induce long term remission with no evidence of disease activity. There are many options that target various mechanisms such as interleukins, inflammatory cytokines and various immune cells. Going into detail about these drugs is beyond what would be expected in your exams. Disease-modifying drug treatment will be coordinated by specialists in multiple sclerosis.
Treating Relapses:
Relapses can be treated with steroids. NICE recommend methylprednisolone:
-500mg orally daily for 5 days
-1g intravenously daily for 3–5 days where oral treatment has failed previously or where relapses are severe
Symptomatic Treatments
It is important to treat the symptoms that result from the disease process along with treating the disease process itself:
- Exercise to maintain activity and strength
- Neuropathic pain can be managed with medication such as amitriptyline or gabapentin
- Depression can be managed with antidepressants such as SSRIs
- Urge incontinence can be managed with anticholinergic medications such as tolterodine or oxybutynin (although be aware these can cause or worsen cognitive impairment)
- Spasticity can be managed with baclofen, gabapentin and physiotherapy
What is motor neurone disease ?
An umbrella term that encompasses a variety of specific diagnoses.
Note: Motor neurone disease is a progressive, ultimately fatal condition where the motor neurones stop functioning. There is no effect on the sensory neurones and patients should not experience any sensory symptoms.
Name some of the different types of MND ?
- Amylotropic lateral sclerosis (AML) is the most common and well known specific type of motor neurone disease. Stephen Hawking had amylotropic lateral sclerosis.
- Progressive bulbar palsy is the second most common form of motor neurone disease. It affects primarily the muscles of talking and swallowing.
- Other types of motor neurone disease to be aware of are progressive muscular atrophy and primary lateral sclerosis.
Pathophysiology of MND ?
There is progressive degeneration of both upper and lower motor neurones. The sensory neurones are spared.
Typical MND patient note:
The typical patient is a late middle aged (e.g. 60) man, possibly with an affected relative. There is an insidious, progressive weakness of the muscles throughout the body affecting the limbs, trunk, face and speech. The weakness is often first noticed in the upper limbs. There may be increased fatigue when exercising. They may complain of clumsiness, dropping things more often or tripping over. They can develop slurred speech (dysarthria).
Signs of lower and upper MND ?
Signs of lower motor neurone disease:
- Muscle wasting
- Reduced tone
- Fasciculations (twitches in the muscles)
- Reduced reflexes
Signs of upper motor neurone disease:
- Increased tone or spasticity
- Brisk reflexes
- Upgoing plantar responses
Diagnosis of MND note:
The diagnosis of motor neurone disease needs to be made very carefully. It is based on the clinical presentation and excluding other conditions that can cause motor neurone symptoms. It should only be made by a specialist when there is certainty. Unfortunately, the diagnosis is often delayed, which causes considerable anxiety and stress.
Management of MND note:
Unfortunately, there are no effective treatments for halting or reversing the progression of the disease.
Riluzole can slow the progression of the disease and extend survival by a few months in AML. It is licensed in the UK and should be initiated by a specialist.
Edaravone is currently used in the United States but not the UK. Recent studies suggest it has the potential to slow the progression of the disease and it may come in to use in the future.
Non-invasive ventilation (NIV) used at home to support breathing at night improves survival and quality of life.
The key to management of the condition is supporting the person and their family:
- Effectively breaking bad news
- Involving the multidisciplinary team (MDT) in supporting and maintaining their quality of life
- Advanced directives to document the patients wishes as the disease progresses
- End of life care planning
- Patients usually die of respiratory failure or pneumonia
What is Parkinson’s disease ?
Parkinson’s disease is a condition where there is a progressive reduction of dopamine in the basal ganglia of the brain, leading to disorders of movement.
Classic triad of features in Parkinson’s disease ?
- Resting tremor
- Rigidity
- Bradykinesia
The symptoms are characteristically asymmetrical, with one side affected more than the other.
Pathophysiology of Parkinson’s ?
The basal ganglia are a group of structures situated in the middle of the brain. They is responsible for coordinating habitual movements such as walking or looking around, controlling voluntary movements and learning specific movement patterns. Part of the basal ganglia called the substantia nigra produces a neurotransmitter called dopamine. Dopamine is essential for the correct functioning of the basal ganglia. In Parkinson’s disease, there is a gradual but progressive fall in the production of dopamine due to the destruction of the substantia nigra.
Presentation of Parkinson’s note:
The typical patient is an older aged man around the age of 70.
Unilateral Tremor:
The tremor in Parkinsons has a frequency of 4-6 Hz, meaning it occurs 4-6 times a second. This is described as a “pill rolling tremor” because it looks like they are rolling a pill between their fingertips and thumb. It is more pronounced when resting and improves on voluntary movement. The tremor is worsened if the patient is distracted. Asking them to do a task with the other hand, such as miming the motion of painting a fence, can exaggerate the tremor.
“Cogwheel” Rigidity:
Rigidity is a resistance to passive movement of a joint. If you take their hand and passively flex and extend their arm at the elbow, you will feel a tension in their arm that gives way to movement in small increments (like little jerks). This is what leads to the cogwheel description.
Bradykinesia
Bradykinesia describes how their movements get slower and smaller. This presents in a number of ways:
- Their handwriting gets smaller and smaller (this is a classic presenting complaint in exams)
- They can only take small steps when walking (“shuffling gait”)
- They have difficulty initiating movement (e.g. from standing still to walking)
- They have difficulty in turning around when standing, having to take lots of little steps
- They have reduced facial movements and facial expressions (hypomimia)
Other Features:
There are a number of other features that often affect patients with Parkinson’s disease:
- Depression
- Sleep disturbance and insomnia
- Loss of the sense of smell (anosmia)
- Postural instability
- Cognitive impairment and memory problems
Tom tip:
A common exam task challenges you to distinguish between the tremor of Parkinson’s disease and benign essential tremor. The table below gives some tips on this:
Parkinson’s Tremor:
- Asymmetrical
- 4-6 hertz
- Worse at rest
- Improves with intentional movement
- Other Parkinson’s features
- No change with alcohol
Benign essential tremor:
- Symmetrical
- 5-8 hertz
- Improves at rest
- Worst with intentional movement
- No other Parkinson’s features
- Improves with alcohol
Parkinson plus syndromes ?
Multiple System Atrophy
This is a rare condition where the neurones of multiple systems in the brain degenerate. It affects the basal ganglia as well as multiple other areas. The degeneration of the basal ganglia lead to a Parkinson’s presentation. The degeneration in other areas lead to autonomic dysfunction (causing postural hypotension, constipation, abnormal sweating and sexual dysfunction) and cerebellar dysfunction (causing ataxia).
Dementia with Lewy Bodies
This is a type of dementia associated with features of Parkinsonism. It causes a progressive cognitive decline. There are associated symptoms of visual hallucinations, delusions, disorders of REM sleep and fluctuating consciousness.
Others
Two other Parkinson’s-plus syndromes exist that involves a number of complex progressive neurological features:
Progressive Supranuclear Palsy
Corticobasal Degeneration
Diagnosis of Parkinson’s note:
Parkinson’s disease is diagnosed clinically based on symptoms and examination. The diagnosis should be made by a specialist with experience in diagnosing Parkinson’s. NICE recommend using the UK Parkinson’s Disease Society Brain Bank Clinical Diagnostic Criteria.
Management of Parkinson’s note:
Treatment is initiated and guided by a specialist, and is tailored to each individual patient and their response to different medications. There is no cure, so treatment is focused on controlling symptoms and minimising side effects.
Patients describe themselves as “on” when the medications are acting and they are moving freely, and “off” when the medications wear out, they have significant symptoms and their next dose is due.
Treatment’s of Parkinson’s ? (for each include how they work and any relevant side effects)
Levodopa
This is synthetic dopamine given orally to boost their own dopamine levels. It is usually combined with a drug that stops levodopa being broken down in the body before it gets the chance to enter the brain. These are peripheral decarboxylase inhibitors. Examples are carbidopa and benserazide.
Combination drugs are:
Co-benyldopa (levodopa and benserazide)
Co-careldopa (levodopa and carbidopa)
Levodopa is the most effective treatment for symptoms but becomes less effective over time. It is often reserved for when other treatments are not managing to control symptoms.
The main side effect of dopamine is when the dose is too high patients develop dyskinesias. Theses are abnormal movements associated with excessive motor activity. Examples are:
Dystonia: This is where excessive muscle contraction leads to abnormal postures or exaggerated movements.
Chorea: These are abnormal involuntary movements that can be jerking and random.
Athetosis: These are involuntary twisting or writhing movements usually in the fingers, hands or feet.
COMT Inhibitors
The main example of this is entacapone. These are inhibitors of catechol-o-methyltransferase (COMT). The COMT enzyme metabolises levodopa in both the body and brain. Entacapone is taken with levodopa (and a decarboxylase inhibitor) to slow breakdown of the levodopa in the brain. It extends the effective duration of the levodopa.
Dopamine Agonists
These mimic dopamine in the basal ganglia and stimulate the dopamine receptors. They are less effective than levodopa in reducing symptoms. They are usually used to delay the use of levodopa and are then used in combination with levodopa to reduce the dose of levodopa that is required to control symptoms. One notable side effect with prolonged use is pulmonary fibrosis. Examples are:
Bromocryptine
Pergolide
Carbergoline
Monoamine Oxidase-B Inhibitors
Monoamine oxidase enzymes break down neurotransmitters such as dopamine, serotonin and adrenaline. The monoamine oxidase-B enzyme is more specific to dopamine and does not act on serotonin or adrenalin. These medications block this enzyme and therefore help increase the circulating dopamine. Similarly to dopamine agonists, they are usually used to delay the use of levodopa and then in combination with levodopa to reduce the required dose. Examples are:
Selegiline
Rasagiline
Benign essential tremor is a relatively common condition associated with older age. It is characterised by what + where is it most notable ?
It is characterised by a fine tremor affecting all the voluntary muscles.
It is most notable in the hands but affects other areas, for example causing a head tremor, jaw tremor and vocal tremor.
6 features of a benign essential tremor ?
- Fine tremor
- Symmetrical
- More prominent on voluntary movement
- Worse when tired, stressed or after caffeine
- Improved by alcohol
- Absent during sleep
Benign essential tremor is diagnosed clinically based on the presenting features. It is important to look for features to exclude other causes of a tremor.
The key differential diagnoses of a tremor are ?
- Parkinson’s disease
- Multiple sclerosis
- Huntington’s Chorea
- Hyperthyroidism
- Fever
- Medications (e.g. antipsychotics)
Management of benign essential tremor ?
There is no definitive treatment for benign essential tremor. The tremor is not harmful and does not require treatment if not causing functional or psychological problems.
Medications that can be tried to improve symptoms are:
- Propranolol (a non-selective beta blocker)
- Primidone (a barbiturate anti-epileptic medication)
Epilepsy note:
Epilepsy is an umbrella term for a condition where there is a tendency to have seizures. Seizures are transient episodes of abnormal electrical activity in the brain. There are many different types of seizures.
A diagnosis of epilepsy is made by a specialist based on the characteristics of the seizure episodes.
2 main ix for epilepsy + any other ix’s ?
- Electroencephalogram (EEG)
- MRI brain - can be used to visualise the structure of the brain. It is used to diagnose structural problems that may be associated with seizures and other pathology such as tumours
Other investigations can be used to exclude other pathology, particularly and ECG to exclude problems in the heart.
Name 6 different types of seizures (excluding status epilepticus) ?
- Generalised Tonic-Clonic Seizures
- Focal Seizures
- Absence Seizures
- Atonic Seizures
- Myoclonic Seizures
- Infantile spasms
What are Generalised Tonic-Clonic seizures, what are the associated symptoms + signs, what happens following the seizure and what is the management ?
These are what most people think of with an epileptic seizure. There is loss of consciousness and tonic (muscle tensing) and clonic (muscle jerking) episodes. Typically the tonic phase comes before the clonic phase. There may be associated tongue biting, incontinence, groaning and irregular breathing.
After the seizure there is a prolonged post-ictal period where the person is confused, drowsy and feels irritable or depressed.
Management of tonic-clonic seizures is with:
- First line: sodium valproate
- Second line: lamotrigine or carbamazepine
Where do focal seizures start, what can they affect, how can they present and how are they managed ?
Focal seizures start in temporal lobes. They affect hearing, speech, memory and emotions. There are various ways that focal seizures can present:
Hallucinations
Memory flashbacks
Déjà vu
Doing strange things on autopilot
One way to remember the treatment is that they are the reverse of tonic-clonic seizures:
- First line: carbamazepine or lamotrigine
- Second line: sodium valproate or levetiracetam
Who do absence seizures typically occur in, what happens, how long do they last and how are they managed ?
Absence seizures typically happen in children. The patient becomes blank, stares into space and then abruptly returns to normal. During the episode they are unaware of their surroundings and won’t respond. These typically only lasts 10-20 seconds. Most patients (> 90%) stop having absence seizures as they get older.
Management is:
-First line: sodium valproate or ethosuximide
What are atonic seizures also known as, what happens in them, how long do they last, when do they begin, what can they be indicative of and how are they managed ?
Atonic seizures are also known as “drop attacks”. They are characterised by brief lapses in muscle tone. These don’t usually last more than 3 minutes. They typically begin in childhood. They may be indicative of Lennox-Gastaut syndrome.
Management is:
- First line: sodium valproate
- Second line: lamotrigine
How do myoclonic seizures present, does the patient remain awake, when do they occur and how are they managed ?
Myoclonic seizures present as sudden brief muscle contractions, like a sudden “jump”. The patient usually remains awake during the episode. They occur in various forms of epilepsy but typically happen in children as part of juvenile myoclonic epilepsy.
Management is:
- First line: sodium valproate
- Other options: lamotrigine, levetiracetam or topiramate
What are Infantile spasms also known as, are they rare, what are they characterised by, what is the prognosis like and how are they treated ?
This is also known as West syndrome. It is a rare (1 in 4000) disorder starting in infancy at around 6 months of age. It is characterised by clusters of full body spasms. There is a poor prognosis: 1/3 die by age 25, however 1/3 are seizure free.
It can be difficult to treat but first line treatments are:
- Prednisolone
- Vigabatrin
Name 5 medications used to treat epilepsy ?
- Sodium valproate
- Carbamazepine
- Phenytoin
- Ethosuximide
- Lamotrigine
What is sodium valproate, how does it work and name 4 notable side effects ?
This is a first line option for most forms of epilepsy (except focal seizures). It works by increasing the activity of GABA, which has a relaxing effect on the brain.
Notable side effects:
- Teratogenic so patients need careful advice about contraception
- Liver damage and hepatitis
- Hair loss
- Tremor
Note: There are a lot of warning about the teratogenic effects of sodium valproate and NICE updated their guidelines in 2018 to reflect this. It must be avoided in girls or women unless there are no suitable alternatives and strict criteria are met to ensure they do not get pregnant.
What is carbamazepine + name 3 notable side effects ?
This is first line for focal seizures. Notable side effects are:
- Agranulocytosis
- Aplastic anaemia
- Induces the P450 system so there are many drug interactions
Name 3 notable side effects of Phenytoin ?
- Folate and vitamin D deficiency
- Megaloblastic anaemia (folate deficiency)
- Osteomalacia (vitamin D deficiency)
Name 2 side effects of ethosuximide ?
- Night terrors
- Rashes
Name 2 side effects of lamotrigine ?
- Stevens-Johnson syndrome or DRESS syndrome. These are life threatening skin rashes
- Leukopenia
Status epilepticus is a medical emergency. What is it ?
Seizures lasting more than 5 minutes or more than 3 seizures in one hour.
Management of status epilepticus (in hospital and in the community) ?
Management of status epileptics in the hospital:
Take an ABCDE approach:
- Secure the airway
- Give high-concentration oxygen
- Assess cardiac and respiratory function
- Check blood glucose levels
- Gain intravenous access (insert a cannula)
- IV lorazepam 4mg, repeated after 10 minutes if the seizure continues
- If seizures persist: IV phenobarbital or phenytoin
Medical options in the community:
- Buccal midazolam
- Rectal diazepam
Neuropathic pain is caused by ?
Abnormal functioning of the sensory nerves, delivering abnormal and painful signals to the brain.
Abnormal sensations form the skin, such as burning, tingling, pins and needles and numbness is called ?
Paresthesia
Neuropathic pain can affect a wide variety of areas with a number of different causes, name 6 of these ?
- Postherpetic neuralgia from shingles is in the distribution of a dermatome and usually on the trunk
- Nerve damage from surgery
- Multiple sclerosis
- Diabetic neuralgia typically affects the feet
- Trigeminal neuralgia
- Complex Regional Pain Syndrome (CRPS)
Features of neuropathic pain ?
- Paresthesia
- Electric shocks
- Loss of sensation to touch of the affected area
Tool used to assess characteristics of pain to determine whether it is likely to be neuropathic + a score of what or more would indicate neuropathic pain ?
DN4 questionnaire.
They are scored out of 10. A score of 4 or more indicates neuropathic pain.
Management of neuropathic pain ? (include other options)
There are four first line treatments for neuropathic pain:
- Amitriptyline is a tricyclic antidepressant
- Duloxetine is an SNRI antidepressant
- Gabapentin is an anticonvulsant
- Pregabalin is an anticonvulsant
NICE recommend using one of these four medications to control neuropathic pain. If that does not work then stop and start an alternative and repeat this until all four have been tried.
Other options:
- Tramadol ONLY as a rescue for short term control of flares
- Capsaicin cream (chilli pepper cream) for localised areas of pain
- Physiotherapy to maintain strength
- Psychological input to help with understanding and coping
What is Trigeminal neuralgia + what is the first line treatment ?
A type of neuropathic pain. Carbamazepine is the first line recommended treatment. If that doesn’t work you should refer to a specialist.
Complex regional pain syndrome note:
This is a condition where areas are affected by abnormal nerve functioning causing neuropathic pain and abnormal sensations. It is usually isolated to one limb. Often it is triggered by an injury to the area.
The area can become very painful and hypersensitive even to simple inputs such as wearing clothing. It can also intermittently swell, change colour, change temperature, flush with blood and have abnormal sweating.
Treatment is often guided by a pain specialist and is similar to other neuropathic pain.
Where does the facial nerve exit the brainstem + where does it pass through on its journey to the face.
At the cerebellopontine angle.
It passes through the temporal bone and parotid gland.
5 branches of facial nerve ?
- Temporal
- Zygomatic
- Buccal
- Marginal mandibular
- Cervical
Function of facial nerve ?
There are three functions of the facial nerve: motor, sensory and parasympathetic.
Motor: Supplies the muscles of facial expression, the stapedius in the inner ear and the posterior digastric, stylohyoid and platysma muscles in the neck.
Sensory: carries taste from the anterior 2/3 of the tongue.
Parasympathetic: it provides the parasympathetic supply to the submandibular and sublingual salivary glands and the lacrimal gland (stimulating tear production).
Unilateral upper motor lesions occur in ?
- Cerebrovascular accidents (strokes)
- Tumours
Bilateral upper motor neurone lesions are rare. They may occur in ?
- Pseudobulbar palsies
- Motor neurone disease
How does Bell’s palsy present + what is the prognosis like ?
It presents as a unilateral lower motor neurone facial nerve palsy.
The majority of patients fully recover over several weeks but recovery may take up to 12 months. A third are left with some residual weakness.
Management of Bell’s palsy ?
- If patients present within 72 hours of developing symptoms, NICE guidelines recommend considering prednisolone as treatment, either:
- 50mg for 10 days
- 60mg for 5 days followed by a 5-day reducing regime of 10mg a day
-Patients also require lubricating eye drops to prevent the eye on the affected drying out and being damaged. If they develop pain in the eye they need ophthalmology review for exposure keratopathy. Tape can be used to keep the eye closed at night.
How does Ramsay-Hunt syndrome present ?
It presents as a unilateral lower motor neurone facial nerve palsy. Patients stereotypically have a painful and tender vesicular rash in the ear canal, pinna and around the ear on the affected side. This rash can extend to the anterior 2/3 of the tongue and hard palate.
What causes Ramsay-Hunt syndrome ?
The herpes zoster virus
Management of Ramsay-Hunt syndrome ?
Treatment should ideally be initiated within 72 hours.
Treatment is with:
- Prednisolone
- Aciclovir
Patients also require lubricating eye drops.
TOM TIP:
Ramsay-Hunt syndrome is a very popular presentation in your MCQ exams. Look out for that patient with a vesicular rash around their ear and a facial nerve palsy.
Other caues of LMN facial nerve palsy ? (arrange into appropriate categories)
Infection:
- Otitis media
- Malignant otitis externa
- HIV
- Lyme’s disease
Systemic disease:
- Diabetes
- Sarcoidosis
- Leukaemia
- Multiple sclerosis
- Guillain–Barré syndrome
Tumours:
- Acoustic neuroma
- Parotid tumours
- Cholesteatomas
Trauma:
- Direct nerve trauma
- Damage during surgery
- Base of skull fractures
Brain tumour note:
Brain tumours are abnormal growths within the brain. There are many different types of brain tumour. They vary from benign tumours (e.g. meningiomas) to highly malignant (e.g. glioblastomas).
Often brain tumours do not have any symptoms, particularly when they are small. As they develop they present with focal neurological symptoms depending on the location of the lesion.
Brain tumours often present with symptoms and signs of raised intracranial pressure. As a tumour grows within the skull it takes up space. This leaves less space for the other contents of the skull (such as the CSF) to squeeze in to and leads to a rise in the pressure within the intracranial space.
TOM TIP:
A common exam question asks the location of the lesion based on the neurology. A popular exam question describes a patient that has had an unusual change in personality and behaviour. This indicates a tumour in the frontal lobe. Remember that the frontal lobe is responsible for personality and higher-level decision making.
Key finding on fundoscopy for raised ICP ?
Papilloedema
Name 4 causes of a raised ICP ?
- Brain tumours
- Intracranial haemorrhage
- Idiopathic intracranial hypertension
- Abscesses or infection
Presentation of raised ICP (concerning features of a headache + other presenting features) ?
Concerning features of a headache that should prompt further examination and investigation include:
- Constant
- Nocturnal
- Worse on waking
- Worse on coughing, straining or bending forward
- Vomiting
Other presenting features of raised intracranial pressure may be:
- Altered mental state
- Visual field defects
- Seizures (particularly focal)
- Unilateral ptosis
- Third and sixth nerve palsies
- Papilloedema (on fundoscopy)
What is papilloedema ?
Swelling of the optic disc secondary to raised ICP
Why does raised ICP cause papilloedema ?
The sheath around the optic nerve is connected with the subarachnoid space. Therefore it is possible for CSF under high pressure to flow into the optic nerve sheath. This increases the pressure around the optic nerve where it connects with the back of the eye at the optic disc, causing optic disc swelling.
Name 5 different types of brain tumours ?
- Secondary metastases
- Gliomas
- Meningiomas
- Pituitary tumours
- Acoustic neuroma (AKA vestibular schwannoma)
Name four common cancers that metastasise to the brain ?
- Lung
- Breast
- Colorectal
- Prostate
What are gliomas, how are they graded, three types to remember form most to least malignant ?
Tumours of glial cells in the brain or spinal cord.
They are graded from 1 to 4 (grade 4 are the most malignant).
Three types to remember:
- Astrocytoma (glioblastoma multiforme is the most common)
- Oligodendroglioma
- Ependymoma
Meningiomas ?
Tumours growing from the cells of the meninges in the brain and spinal cord. They are usually benign, however they take up space and this mass effect can lead to raised intracranial pressure and neurological symptoms.
Are pituitary tumours usually benign or malignant ?
Usually benign
If pituitary tumours grow large enough they can compress on what and what does this cause ?
They can compress on the optic chiasm causing a specific visual field defect called a bitemporal hemianopia.
What other problems do pituitary tumour cause, give examples where appropriate ?
They have the potential to cause hormone deficiencies (hypopituitarism) or to release excessive hormones leading to:
- Acromegaly
- Hyperprolactinaemia
- Cushing’s disease
- Thyrotoxicosis
What are acoustic neuromas ?
Tumours of the schwann cells surrounding the auditory nerve that innervates the inner ear.
Where do acoustic neuromas occur ?
Around the cerebellopontine angle.
Acoustic neuromas are slow growing but eventually grow large enough to produce symptoms and become dangerous. Are they usually unilateral or bilateral ?
Usually unilateral.
Note: Bilateral acoustic neuromas are associated with neurofibromatosis type 2
3 classic symptoms of an acoustic neuroma + what else can they be associated with ?
- Hearing loss
- Tinnitus
- Balance problems
They can be associated with a facial nerve palsy
Note:
There is massive variation in brain tumours from completely benign to extremely malignant. Surgery is dependent on the grade and behaviour of the brain tumour.
Management options include:
- Palliative care
- Chemotherapy
- Radiotherapy
- Surgery
Treatment of pituitary tumours ? (4 points)
- Trans-sphenoidal surgery
- Radiotherapy
- Bromociptine to block prolactin secreting tumours
- Somatostatin analogues (e.g. ocreotide) to block growth hormone secreting tumours
What is Huntington’s Chorea ?
An autosomal dominant genetic condition that causes a progressive deterioration in the nervous system. Patients are usually asymptomatic until symptoms begin around aged 30 to 50.
Huntington’s chorea is a ……. ……. ……. that involves a genetic mutation in the ……….. on chromosome …. ??
“trinucleotide repeat disorder”
HTT gene
4
Huntington’s chorea displays something called genetic “anticipation”. Anticipation is a feature of trinucleotide repeat disorders. This is where successive generations have more repeats in the gene, resulting in what ?
- An earlier age of onset
- Increased severity of disease
TOM TIP:
Anticipation is a common topic of exam questions. It is worth remembering the features and connection with Huntington’s for your exams.
Presentation of Huntington’s chorea ?
It usually presents with an insidious, progressive worsening of symptoms. It typically begins with cognitive, psychiatric or mood problems. These are followed by the development of movement disorders;
- Chorea (involuntary, abnormal movements)
- Eye movement disorders
- Dysarthria
- Dysphagia
Diagnosis of Huntington’s ?
Diagnosis is made in a specialist genetic centre using a genetic test for the faulty gene. It involves pre-test and post-test counselling regarding the implications of the results.
Management of Huntington’s note:
There are currently no treatment options for slowing or stopping the progression of the disease.
The key to management of the condition is supporting the person and their family:
-Effectively breaking bad news
-Involvement of MDT in supporting and maintaining their quality of life (e.g. occupational therapy, physiotherapy and psychology)
-Speech and language therapy where there are speech and swallowing difficulties
-Genetic counselling regarding relatives, pregnancy and children
-Advanced directives to document the patients wishes as the disease progresses
End of life care planning
Medical treatment is based on symptomatic relief. As the disease progresses medication requirements may change. It is important to discontinue unnecessary medication to minimise adverse effects.
Medications that can suppress the disordered movement:
- Antipsychotics (e.g. olanzapine)
- Benzodiazepines (e.g. diazepam)
- Dopamine-depleting agents (e.g. tetrabenazine)
Depression can be treated with antidepressants.
Prognosis of Huntington’s ?
Huntington’s chorea is a progressive condition. Life expectance is around 15-20 years after the onset of symptoms. As the disease progresses patients become more susceptible and less able to fight off illnesses. Death is often due to respiratory disease (e.g. pneumonia). Suicide is a more common cause of death than in the general population.
What is myasthenia gravis ?
Myasthenia graves is an autoimmune condition that causes muscle weakness that gets progressively worse with activity and improves with rest.
Typical ages at which pts experience myastenia gravis ? (both male and female)
Myasthenia gravis affects men and women at different ages. Typical patients are either a woman under the age of 40 or a man over the age of 60.
There is a strong link between myasthenia gravis and what ?
Thymoma
Pathophysiology of myasthenia gravis ?
In around 85% of patients with myasthenia gravis, acetylcholine receptor antibodies are produced by the immune system. These bind to the postsynaptic neuromuscular junction receptors. This blocks the receptor and prevents the acetylcholine from being able to stimulate the receptor and trigger muscle contraction. As the receptors are used more during muscle activity, more of them become blocked up. This leads to less effective stimulation of the muscle with increased activity. There is more muscle weakness the more the muscles are used. This improves with rest as more receptors are freed up for use again.
These antibodies also activate the complement system within the neuromuscular junction, leading to damage to cells at the postsynaptic membrane. This further worsens the symptoms.
There are two other antibodies that cause the other 15% of cases of myasthenia gravis. These are antibodies against muscle-specific kinase (MuSK) and antibodies against low-density lipoprotein receptor-related protein 4 (LRP4). MuSK and LRP4 and important proteins for the creation and organisation of the acetylcholine receptor. Destruction of these proteins by autoantibodies leads to inadequate acetylcholine receptors. This causes the symptoms of myasthenia gravis.
Presentation of myasthenia gravis ?
The severity of symptoms can vary dramatically between patients. They can be mild and subtle or life threateningly severe. The characteristic feature is weakness that gets worse with muscle use and improves with rest. Symptoms are typically minimal in the morning and worst at the end of the day.
The symptoms most affect the proximal muscles and small muscles of the head and neck. It leads to:
- Extraocular muscle weakness causing diplopia
- Eyelid weakness causing ptosis
- Weakness in facial movements
- Dysphagia
- Fatigue in the jaw when chewing
- Dysarthria
- Progressive weakness with repetitive movements
What should you include in your examination if you suspect myasthenia gravis ?
There are a few ways to elicit fatiguability in the muscles:
- Repeated blinking will exacerbate ptosis
- Prolonged upward gazing will exacerbate diplopia on further eye movement testing
- Repeated abduction of one arm 20 times will result in unilateral weakness when comparing both sides
Check for a thymectomy scar.
Test the forced vital capacity (FVC).
Diagnosis of myasthenia gravis ?
Diagnosis can be made testing directly for the relevant antibodies:
- Acetylcholine receptor (ACh-R) antibodies (85% of patients)
- Muscle-specific kinase (MuSK) antibodies (10% of patients)
- LRP4 (low-density lipoprotein receptor-related protein 4) antibodies (less than 5%)
A CT or MRI of the thymus gland is used to look for a thymoma.
The edrophonium test can be helpful where there is doubt about the diagnosis
Edrophonium test ?
Patients are given an IV dose of edrophonium chloride (or neostigmine). Normally, cholinesterase enzymes in the neuromuscular junction break down acetylcholine. Edrophonium block these enzymes and stop the breakdown of acetylcholine. As a result the level of acetylcholine at the neuromuscular junction increases. It briefly and temporarily relieves the weakness. This establishes a diagnosis of myasthenia gravis.
Management of myasthenia gravis ?
- Reversible acetylcholinesterase inhibitors (usually pyridostigmine or neostigmine) increases the amount of acetylcholine in the neuromuscular junction and improve symptoms
- Immunosuppression (e.g. prednisolone or azathioprine) suppresses the production of antibodies
- Thymectomy can improve symptoms even in patients without a thymoma
Monoclonal antibodies:
- Rituximab is a monoclonal antibody that targets B cells and reduces the production of antibodies. It is available on the NHS if standard treatment is not effective and certain criteria are met.
- Eculizumab is a monoclonal antibody that targets complement protein C5. This could potentially prevent the complement activation and destruction of acetylcholine receptors. There is ongoing research and debate about whether the evidence is strong enough to offer it on the NHS. It is currently not recommended by NICE.
What is a myasthenic crisis ?
A severe complication of myasthenia gravis. It can be life threatening. It causes an acute worsening of symptoms, often triggered by another illness such as a respiratory tract infection. This can lead to respiratory failure as a result of weakness in the muscle of respiration
Management of a myasthenic crisis ?
Patients may require non-invasive ventilation with BiPAP or full intubation and ventilation.
Medical treatment is with immunomodulatory therapies such as IV immunoglobulins and plasma exchange.
Lambert-Eaton myasthenic syndrome has a similar set of features to ?
Myasthenia gravis
Lambert-Eaton myasthenic syndrome results in ?
Progressive muscle weakness with increased use
How do the symptoms of Lambert-Eaton myasthenic syndrome compare to myasthenia gravis ?
The symptoms tend to be more insidious and less pronounced than in myasthenia gravis.
Lambert-Eaton syndrome typically occurs in patients with what condition ?
Small-cell lung cancer
Pathophysiology of Lambert-Eaton myasthenic syndrome ?
It is a result of antibodies produced by the immune system against voltage-gated calcium channels in small cell lung cancer (SCLC) cells. These antibodies also target and damage voltage-gated calcium channels in the presynaptic terminals of the neuromuscular junction where motor nerves communicate with muscle cells.
These voltage-gated calcium channels are responsible for assisting in the release of acetylcholine into the synapse of the neuromuscular junction. This acetylcholine then binds to the acetylcholine receptors and stimulates a muscle contraction. When these channels are destroyed, less acetylcholine is release into the synapse.
Presentation of Lambert-Eaton myasthenic syndrome ?
Symptoms tend to develop slowly. The proximal muscles are most notably affected causing proximal muscle weakness.
It can also affect
- The intraocular muscles causing DIPLOPIA
- The levator muscles in the eyelid causing PTOSIS
- The oropharyngela muscles causing slurred speech and DYSPHAGIA
This weakness is worse with prolonged use of the muscles
Management of Lambert-Eaton myasthenic syndrome ?
It is important to diagnose and manage any underlying malignancy. In older smokers with symptoms of Lambert-Eaton syndrome consider investigating for small cell lung cancer.
Amifampridine allows more acetylcholine to be released in the neuromuscular junction synapses. It works by blocking voltage-gated potassium channels in the presynaptic cells, which in turn prolongs the depolarisation of the cell membrane and assists calcium channels in carrying out their action. This improves symptoms in Lambert-Eaton syndrome.
Other options:
- Immunosuppressants (e.g. prednisolone or azathioprine)
- IV immunoglobulins
- Plasmapheresis
What is Charcot-Marie-Tooth disease ?
An inherited disease that affects the peripheral motor and sensory nerves.
Note:
There are various types of Charcot-Marie-Tooth with different genetic mutations and different pathophysiology. They cause dysfunction in the myelin or the axons. The majority of mutations are inherited in an autosomal dominant pattern. Symptoms usually start to appear before the age of 10 years but the onset of symptoms can be delayed until 40 or later.
Classical features of Charcot-Marie-Tooth to look out for when examining a patient ?
Note: Not all of these features will apply to all patients with the condition but they are a helpful set of features to look out for, particularly in your OSCEs:
- High foot arches (pes cavus)
- Distal muscle wasting causing “inverted champagne bottle legs”
- Weakness in the lower legs, particularly loss of ankle dorsiflexion
- Weakness in the hands
- Reduced tendon reflexes
- Reduced muscle tone
- Peripheral sensory loss
Causes of peripheral neuropathy ?
A – Alcohol B – B12 deficiency C – Cancer and Chronic Kidney Disease D – Diabetes and Drugs (e.g. isoniazid, amiodarone and cisplatin) E – Every vasculitis
TOM TIP:
A patient presenting with Charcot-Marie-Tooth disease is a common OSCE scenario. You will have to perform a neurological examination on a patient that has a peripheral neuropathy. Charcot-Marie-Tooth is a relatively common (1 in 2,500 people) condition with good signs that has a high chance of appearing in your exams. Look for the other features, suggest the diagnosis, then run through the ABCDE mnemonic to suggest the possible other causes.
Management of Charcot-Marie-Tooth disease ?
There is no treatment to alter the underlying disease or prevent it progressing. Management is purely supportive with input from various members of the multidisciplinary team:
- Neurologists and geneticists to make the diagnosis
- Physiotherapists to maintain muscle strength and joint range of motion
- Occupational therapists to assist with activities of living
- Podiatrists to help with foot symptoms and suggest insoles and other orthoses to improve symptoms
- Orthopaedic surgeons to correct disabling joint deformities
What is Guillain-Barré syndrome, what does it cause and what is it triggered by ?
It is an “acute paralytic polyneuropathy” that affects the peripheral nervous system. It causes acute, symmetrical, ascending weakness and can also cause sensory symptoms. It is usually triggered by an infection and is particularly associated with to campylobacter jejuni, cytomegalovirus and Epstein-Barr virus.
Pathophysiology of Guillain-Barré syndrome ?
Guillain-Barré is thought to occur due to a process called molecular mimicry. The B cells of the immune system create antibodies against the antigens on the pathogen that causes the preceding infection. These antibodies also match proteins on the nerve cells. They may target proteins on the myelin sheath of the motor nerve cell or the nerve axon.
Presentation of Guillain-Barré syndrome ?
- Symmetrical ascending weakness (starting at the feet and moving up the body)
- Reduced reflexes
- There may be peripheral loss of sensation or neuropathic pain
- It may progress to the cranial nerves and cause facial nerve weakness
Clinical course of Guillain-Barré syndrome ?
Symptoms usually start within 4 weeks of the preceding infection. The symptoms typically start in the feet and progresses upward. Symptoms peak within 2-4 weeks, then there is a recovery period that can last months to years.
Diagnosis of Guillain-Barré syndrome ?
A diagnosis of Guillain-Barré syndrome is made clinically. The Brighton criteria can be used for diagnosis.
Diagnosis can be supported by investigations:
- Nerve conduction studies (reduced signal through the nerves)
- Lumbar puncture for CSF (raised protein with a normal cell count and glucose)
Management of Guillain-Barré syndrome ?
- IV immunoglobulins
- Plasma exchange (alternative to IV IG)
- Supportive care
- VTE prophylaxis (pulmonary embolism is a leading cause of death)
In severe cases with respiratory failure patients may need intubation, ventilation and admission to the intensive care unit.
Prognosis of Guillain-Barré syndrome ?
- 80% will fully recover
- 15% will be left with some neurological disability
- 5% will die
What is neurofibromatosis ?
A genetic condition that causes nerve tumours (neuromas) to develop throughout the nervous system. These tumours are benign, however they do cause neurological and structural problems
Different types of neurofibromatosis ?
Type 1 and type 2.
NF1 ?
The NF1 gene is found on chromosome 17. It codes for a protein called neurofibromin which is a tumour suppressor protein. Inheritance of this gene is AD.
Criteria for diagnosing NF1 ?
There must be at least 2 of the 7 features to indicate a diagnosis. You can remember this with the mnemonic CRABBING.
C – Café-au-lait spots (6 or more) measuring ≥ 5mm in children or ≥ 15mm in adults
R – Relative with NF1
A – Axillary or inguinal freckles
BB – Bony dysplasia such as Bowing of a long bone or sphenoid wing dysplasia
I – Iris hamartomas (Lisch nodules) (2 or more) are yellow brown spots on the iris
N – Neurofibromas (2 or more) or 1 plexiform neurofibroma
G – Glioma of the optic nerve
Investigations for neurofibromatosis type 1 ?
Diagnosis is based on clinical criteria and no investigations are required to make a definitive diagnosis.
Genetic testing can be used where there is doubt.
Xrays can be used to investigate bone pain and bone lesions.
Imaging with CT and MRI scans can be used to investigate lesions in the brain, spinal cord and elsewhere in the body.
Management of NF1 ?
There is no treatment of the underlying disease process or to prevent the development of neurofibromas or complications.
Management is to control symptoms, monitor the disease and treat complications.
Complications of NF1 ?
- Migraines
- Epilepsy
- Renal artery stenosis causing hypertension
- Learning and behavioural problems (e.g. ADHD)
- Scoliosis of the spine
- Vision loss (secondary to optic nerve gliomas)
- Malignant peripheral nerve sheath tumours
- Gastrointestinal stromal tumour (a type of sarcoma)
- Brain tumours
- Spinal cord tumours with associated neurology (e.g. paraplegia)
- Increased risk of cancer (e.g. breast cancer)
- Leukaemia
Neurofibromatosis type 2 note:
The neurofibromatosis type 2 gene is found on chromosome 22. It codes for a protein called merlin, which is a tumour suppressor protein particularly important in Schwann cells. Mutations in this gene lead to the development of schwannomas (benign nerve sheath tumours of the Schwann cells). Inheritance is autosomal dominant.
Neurofibromatosis type 2 is most associated with what + what are the symptoms of this ?
Neurofibromatosis type 2 is most associated with acoustic neuromas. These are tumours of the auditory nerve innervating the inner ear.
Symptoms of an acoustic neuroma are:
- Hearing loss
- Tinnitus
- Balance problems
Note: Schwannomas can also develop in the brain and spinal cord with symptoms based on the location of the lesion.
Surgery can be used to resect tumours although there is a risk or permanent nerve damage.
TOM TIP:
Bilateral acoustic neuromas almost certainly indicate neurofibromatosis type 2. This is a popular association in exams so worth remembering.
Tuberous sclerosis is a genetic condition that causes features in multiple systems. What is its characteristic feature ?
The development of hamartomas
What are hamartomas ?
Benign neoplastic growths of the tissue that they originate from
Hamartomas commonly affect the ?
- Skin
- Brain
- Lungs
- Heart
- Kidneys
- Eyes
Tuberous sclerosis is caused by mutations in which two genes and what do they both code for ?
- TSC1 gene on chromosome 9, which codes for hamartin
- TSC2 gene on chromosome 16, which codes for tuberin
What do hamartin and tuberin do ?
Interact with each other to control the size and growth of cells. Abnormalities in one of these proteins leads to abnormal cell size and growth.
Skin signs of tuberous sclerosis ?
- Ash leaf spots are depigmented areas of skin shaped like an ash leaf
- Shagreen patches are thickened, dimpled, pigmented patches of skin
- Angiofibromas are small skin coloured or pigmented papules that occur over the nose and cheeks
- Subungual fibromata are fibromas growing from the nail bed. They are usually circular painless lumps that grow slowly and displace the nail
- Cafe-au-lait spots are light brown “coffee and milk” coloured flat pigmented lesions on the skin
- Poliosis is an isolated patch of white hair on the head, eyebrows, eyelashes or beard
Neurological + other features of tuberous sclerosis
Neurological features:
- Epilepsy
- Learning disability and developmental delay
Other features:
- Rhabdomyomas in the heart
- Gliomas (tumours of the brain and spinal cord)
- Polycystic kidneys
- Lymphangioleiomyomatosis (abnormal growth in smooth muscle cells, often affecting the lungs. These can cause cough, SOB, chest pain, haemoptysis and pneumothorax)
- Retinal hamartomas
Tuberous sclerosis presentation note:
The classical presentation is a child presenting with epilepsy found to have skin features of tuberous sclerosis. It can also present in adulthood.
Tuberous sclerosis management note:
Management is supportive with monitoring and treating complications such as epilepsy. There is no treatment for the underlying gene defect.
Differential diagnoses of headache ?
- Tension headaches
- Migraines
- Cluster headaches
- Secondary headaches
- Sinusitis
- Giant cell arteritis
- Glaucoma
- Intracranial haemorrhage
- Subarachnoid haemorrhage
- Analgesic headache
- Hormonal headache
- Cervical spondylosis
- Trigeminal neuralgia
- Raised intracranial pressure (brain tumours)
- Meningitis
- Encephalitis
Red flag symptoms in someone presenting with a headache, state the conditions that these symptoms could indicate ?
- Fever, photophobia or neck stiffness (meningitis or encephalitis)
- New neurological symptoms (haemorrhage, malignancy or stroke)
- Dizziness (stroke)
- Visual disturbance (temporal arteritis or glaucoma)
- Sudden onset occipital headache (subarachnoid haemorrhage)
- Worse on coughing or straining (raised intracranial pressure)
- Postural, worse on standing, lying or bending over (raised intracranial pressure)
- Severe enough to wake the patient from sleep
- Vomiting (raised intracranial pressure or carbon monoxide poisoning)
- History of trauma (intracranial haemorrhage)
- Pregnancy (pre-eclampsia)
TOM TIP:
Practice asking red flag questions so you can demonstrate in an exam that you are thinking about serious causes. This will score extra points and also help you document well when you start seeing patients.
Presentation of tension headaches ?
Classically produce a mild ache across the forehead and in a band-like pattern around the head.
They come on and resolve gradually and don’t produce visual changes
Name 5 associations of tension headaches ?
- Stress
- Depression
- Alcohol
- Skipping meals
- Dehydration
Treatment of tension headaches ?
- Reassurance
- Basic analgesia
- Relaxation techniques
- Hot towels to local area
What are secondary headaches ?
Secondary headaches give a similar presentation to a tension headache but with a clear cause.
Name 4 causes of a secondary headache ?
- Underlying medical conditions such as infection, obstructive sleep apnoea or pre-eclampsia
- Alcohol
- Head injury
- Carbon monoxide poisoning
Hormonal headache note:
Hormonal headaches are related to oestrogen. The produce a generic, non-specific, tension-like headache.
They tend to be related to low oestrogen:
- Two days before and first three days of the menstrual period
- Around the menopause
- Pregnancy. It is worse in the first few weeks and improves in the last 6 months. Headaches in the second half of pregnancy should prompt investigation for pre-eclampsia.
The oral contraceptive pill can improve hormonal headaches.
Cervical spondylosis note:
Cervical spondylosis is a common condition caused by degenerative changes in the cervical spine. It causes neck pain, usually made worse by movement. However, if often presents with headache.
It is important to exclude other causes of neck pain such as inflammation, malignancy and infection. It is also important to exclude spinal cord or nerve root lesions.
Which three branches make up the trigeminal nerve ?
- Ophthalmic (V1)
- Maxillary (V2)
- Mandibular (V3)
Trigeminal neuralgia note:
Trigeminal neuralgia can affect any combination of the branches. The cause is unclear but it is thought to be caused by compression of the nerve. 90% of cases are unilateral, 10% are bilateral. Around 5-10% of people with multiple sclerosis have trigeminal neuralgia.
Presentation of trigeminal neuralgia ?
It presents with intense facial pain that comes on spontaneously and last anywhere between a few seconds to hours. It is often described as an electricity-like shooting pain. Attacks often worsen over time.
Note: There are a number of possible triggers for the pain in patients with trigeminal neuralgia. These include things like cold weather, spicy food, caffeine and citrus fruits.
Management of trigeminal neuralgia ?
NICE recommend carbamazepine as first-line for trigeminal neuralgia. Surgery to decompress or intentionally damage the trigeminal nerve is an option.
Name 4 types of migraine ?
- Migraine without aura
- Migraine with aura
- Silent migraine (migraine with aura but without a headache)
- Hemiplegic migraine
Migraine headaches last between 4 and 72 hours. Typical features are ? (7 points)
- Moderate to severe intensity
- Pounding or throbbing in nature
- Usually unilateral but can be bilateral
- Photophobia
- Phonophobia
- With or without aura
- Nausea and vomiting
Aura is the term used to describe the visual changes associated with migraines. There can be multiple different types of aura, name 4 of these ?
- Sparks in vision
- Blurring vision
- Lines across vision
- Loss of different visual fields
Hemiplegic migraines can mimic stroke. It is essential to act fast and exclude a stroke in patients presenting with symptoms of hemiplegic migraine.
Symptoms of a hemiplegic migraine can vary significantly. They can include what ? (5 points)
Typical migraine symptoms Sudden or gradual onset Hemiplegia (unilateral weakness of the limbs) Ataxia Changes in consciousness
Triggers of migraines ?
- Stress
- Bright lights
- Strong smells
- Certain foods (e.g. chocolate, cheese, caffeine)
- Dehydration
- Menstruation
- Abnormal sleep patterns
- Trauma
Acute management of migraines ?
Patients often develop their own patterns for helping to relieve their symptoms. Often patients will go to a dark quiet room and sleep.
Options for medical management are:
- Paracetamol
- Triptans (e.g. sumatriptan 50mg as the migraine starts)
- NSAIDs (e.g ibuprofen or naproxen)
- Antiemetics if vomiting occurs (e.g. metoclopramide)
Which class of drugs are triptans ?
5HT receptor agonists
Migraine prophylaxis ?
Keeping a headache diary can help identify triggers
Certain medications can be used long term to reduce the frequency and severity of attacks:
- Propranolol
- Topiramate (this is teratogenic and can cause a cleft lip/palate so patients should not get pregnant)
- Amitriptyline
Acupuncture is an option recommended by NICE recommend for the treatment of migraines. It is reported to be as effective as prophylactic medications.
Supplementation with vitamin B2 (riboflavin) may reduce frequency and severity.
In migraine specifically triggered around menstruation then prophylaxis with NSAIDS (e.g. mefanamic acid) or triptans (frovatriptan or zolmitriptan) can be used around that time as a preventative measure.
Migraines tend to get better over time and people often go in to remission from their symptoms.
What are cluster headaches ?
Severe and unbearable unilateral headaches, usually around the eye
Where does the name cluster headaches come from ?
The headaches come in clusters of attacks and then disappear for a while.
For example, a patient may suffer 3 – 4 attacks a day for weeks or months followed by a pain-free period lasting 1-2 years. Attacks last between 15 minutes and 3 hours.
Note:
A typical patient with cluster headaches in your exams is a 30 – 50 year-old male smoker. Attacks can be triggered by things like alcohol, strong smells and exercise.
Cluster headaches are often described as one of the most severe and intolerable pains in the world. They are sometimes referred to as “suicide headaches” due to the severity of the pain.
What’re the symptoms of cluster headaches ?
Symptoms are typically all unilateral:
- Red, swollen and watering eye
- Miosis
- Ptosis
- Nasal discharge
- Facial sweating
Treatment options for cluster headaches ? (acute and prophylactic)
Acute management:
- Triptans (e.g. sumatriptan 6mg injected subcutaneously)
- High flow 100% oxygen for 15-20 minutes (can be given at home)
Prophylaxis options:
- Verapamil
- Lithium
- Prednisolone (a short course for 2-3 weeks to break the cycle during clusters)
